Certain DNA polymerizing and purine nucleotide metabolizing enzymes are uniquely important in lymphoid differentiation and offer possibilities for cytochemical analysis. These enzymes represent a set of intracellular markers which will be evaluated in terms of stage of differentiation of normal and malignant lymphoid cells. Terminal deoxynucleotidyl transferase appears to be a marker specifically related to certain classes of poorly differentiated lymphoblasts. Use of specific antisera to terminal transferase permits easy cytological identification of individual cells containing the enzyme. Deficiencies of adenosine deaminase and purine nucleoside phosphorylase are associated with severe lymphopenia and immunodeficiency. Immunospecific reagents for detection of adenosine deaminase and purine nucleoside phosphorylase can also be employed in immunocytochemistry. Antisera will be labeled for use in immunofluorescent and immunoperoxidase techniques. Production of a battery of highly specific antisera to human enzymes is a goal of this project. These sera will be employed to define the molecular pathology of a variety of diseases ranging from malignancies such as leukemia and lymphoma to immunodeficiency syndromes. Immunocytochemical techniques will be tested as methods of identifying small numbers of malignant lymphoid cells in a large population of normal cells. Such procedures should be especially valuable in detection of residual malignant cells in patients who have been treated for acute lymphoblastic leukemia or lymphoma. The overall project is an integrated collaborative study of human disease utilizing the skills of biochemists, immunologists, pathologists and clinicians.